JPH0149501B2 - - Google Patents

Description

[Detailed description of the invention]

"Technical Field" The present invention is used in dentistry, oral surgery, orthopedics, otorhinolaryngology, etc. to fill in bone defects caused by surgery for diseases such as accidental fractures, bone tumors, and alveolar pyorrhea. The present invention relates to a calcium phosphate-based porous bone filling material. "Prior Art and its Problems" Many research and developments have been conducted since ancient times to replace and compensate for missing biological hard tissues. Classifying these prosthetic materials from the viewpoint of materials, they are broadly divided into those using natural bone and those using artificial materials. Substitute materials using natural bone include autologous bone that uses the patient's normal bone, allogeneic bone that uses the normal bone of a close relative or cryopreserved bone of a deceased person, and bone from cows, pigs, etc. There are different types of bones that utilize However, although autologous bone does not cause rejection after transplantation, it requires harvesting bone tissue from the patient's normal site, which places a heavy burden on the patient, and it is not possible to harvest a sufficient amount of bone tissue. However, even when using the bone of a close relative who is less likely to experience rejection, the burden is not reduced because surgery on another living body is required to harvest the bone tissue, and there is a risk of rejection. is also unavoidable. Furthermore, preserved bones of deceased persons or foreign bones such as calf bones from which proteins have been removed have the fatal drawback of strong foreign body reactions in vivo. On the other hand, artificial filling materials include metals such as cobalt-chromium, titanium, and stainless steel, ceramics such as alumina, zirconia, tricalcium phosphate, hydroxyapatite, and calcium phosphate glass, and polymer materials such as silicone resin. , carbon, etc. are used. Among these, ceramics are stable in vivo and have excellent biocompatibility, so their application as medical materials has been attempted and put into practical use in recent years. Ceramics can be further classified as medical materials, especially bone filling materials, into bioinert and bioactive materials. Bioinertness means that the implanted medical material does not cause any reaction with the surrounding hard tissue, and bioactivity means that the implanted medical material has a direct bond with new bone. . Examples of bioinert materials include alumina and zirconia, while examples of bioactive materials include calcium phosphate materials such as calcium triphosphate, hydroxyapatite, and calcium phosphate glasses. Recently, calcium phosphate sintered bodies, especially hydroxyapatite sintered bodies, which are bioactive ceramics, have been evaluated for their excellent biocompatibility and have been commercialized as artificial tooth roots. Furthermore, bone grafting materials have already been developed in which hydroxyapatite sintered bodies have a porous structure, improve body fluid circulation, cause calcification in the pores, and combine with new bone. This calcium phosphate-based porous bone grafting material is one of the materials that is currently attracting the most attention as a bone grafting material, and various porous sintered bodies with characteristics in their pore morphology have been proposed (Japanese Patent Laid-Open No. 1989-1999). -16879, JP-A-60-21763, etc.). Here, the pore morphology, etc. of these conventional porous sintered bodies was designed with the aim of increasing compatibility with surrounding bone and mechanical strength, and in these respects, considerable evaluation cannot be given. However, when considering a porous sintered body as a bone grafting material, its workability is one of the important factors, and there is still room for further improvement in this respect. In other words, when performing bone graft implant surgery, detailed trimming is essential before and during surgery, and calcium phosphate ceramics are relatively easy to process among ceramics, and diamond burs, diamond disks, etc. are used to process them. Although grinding and cutting are possible, the difficulty of trimming large areas has arisen. "Object of the Invention" An object of the present invention is to provide a calcium phosphate-based porous bone grafting material that has excellent biocompatibility and better processability. "Structure of the Invention" The above object is achieved by a calcium phosphate-based porous bone substitute material characterized by having continuous pores with an average pore diameter of 0.01 to 2000 μm and independent pores with an average pore diameter of 0.01 to 30 μm. . The present inventors previously discovered that the capsule reaction, which is one of the foreign body reactions to bone grafting materials implanted in living bodies, is caused by macrophages and phagocytic cells such as osteoclasts attached to bone grafting materials. Capsule reaction As an excellent bone substitute material that promotes mineralization of new bone without causing
We have found a bone grafting material that has continuous pores of 0.01 to 50 μm. Now, regarding a bone graft material having such a continuous hole, when considering workability such as trimming during surgery, it is possible to increase the porosity of the continuous hole to lower mechanical strength and improve workability. However, at the same time, the pore diameter becomes large and the continuity of the bone grafting material on the machined surface decreases, making it brittle and easily crumbling, making it unsuitable as a bone grafting material. Therefore, as a result of further intensive research, the present inventors have found that by adding fine independent pores to the bone grafting material having continuous pores as described above, the continuity of the bone grafting material can be maintained and the average pore diameter can be increased. It was discovered that only the processability could be improved without increasing the processability, and the present invention was completed. In addition, in the bone grafting material of the present invention, the average pore diameter of the continuous pores is not limited to the range of 0.01 to 50 μm described above as being effective in preventing capsule reactions. In other words, a pore size in this range is particularly preferable when the bone grafting material is relatively small such as granules, but a bone grafting material with a large volume has a pore size in this range. It has been found that even if there are communicating pores, the circulation of body fluids is poor, and there is not much space for bone formation, and the synthesis with new bone is delayed.In general, the average pore diameter is in the range of 0.01 to 2000 μm. It has become clear that continuous pores provide a site for bone formation and at the same time prevent capsule reaction. In the bone grafting material of the present invention, the average pore diameter of the closed pores is 0.01 to 30 μm, more preferably 0.01 to 20 μm.
It is said that That is, if the pore size is less than 0.01 μm, it is difficult to form discontinuous independent pores, whereas if the pore size is more than 30 μm, the strength may decrease. In a preferred embodiment of the present invention, the total porosity of the continuous pores and independent pores is preferably 5 to 75%. This is because if the total porosity is less than 5%, the workability will decrease, and if the total porosity exceeds 75%, the strength will decrease and it will be easy to collapse. In addition, the ratio of continuous pores to the total pores is
It is preferably 10.0 to 99.6%. If the proportion of continuous pores is less than 10.0%, sufficient circulation of body fluids will not be achieved, and if the proportion of continuous pores exceeds 99.6%, the effect of independent pores will hardly appear. As the calcium phosphate material for achieving the bone filling material of the present invention, various known materials can be used, but hydroxyapatite, calcium triphosphate, etc. are particularly preferred. In order to manufacture the bone grafting material of the present invention, a known method for manufacturing a bone grafting material having communicating holes may be carried out with some modifications. There are typically the following four methods for manufacturing bone grafting materials having continuous holes. That is, the first method is a method in which a foaming agent such as hydrogen peroxide or egg albumin is added to a calcium phosphate-based raw material slurry, foamed, dried, and baked at 900 to 1400 ° C.
The second method is to attach a calcium phosphate-based raw material slurry to a thermally decomposable material having interconnected pores and fire it at 900 to 1400°C.The third method is to attach beads of a thermally decomposable material to a calcium phosphate-based raw material powder. and molded with a press etc. at 900~1400℃
A fourth method is to granulate the calcium phosphate-based raw material powder using a rolling granulator, bind the resulting granules with an organic binder such as polyvinyl alcohol, and granulate as necessary. 900～
One example is a method of firing at 1400°C. The closed pores in the bone grafting material of the present invention can be applied to any of the bone grafting materials produced by the above four methods, but in consideration of manufacturing cost and productivity, the first method is used, that is, by foaming a calcium phosphate-based raw material slurry. It is preferable to apply it to a bone grafting material obtained by drying. In this first method, one embodiment for providing discontinuous pores is to add beads of a pyrolyzable material to a calcium phosphate slurry foamed by a foaming agent. For example, pyrolyzable beads with an average particle diameter of 0.02 to 40 μm, more preferably 0.02 to 30 μm, in an amount of 0.1 to 30% by weight based on the calcium phosphate raw material are added to a slurry containing a calcium phosphate raw material, and this mixed slurry is By adding a foaming agent such as hydrogen peroxide or egg albumin, foaming, drying, and baking, a desired bone grafting material having both open and closed pores can be obtained. In addition, the amount of thermally decomposable substance added is 0.1
If it is less than 30% by weight, the processability of the resulting bone grafting material cannot be improved, while if it exceeds 30% by weight, the strength of the resulting bone grafting material will decrease, making it impractical. Further, as the thermally decomposable substance to be added, synthetic resin beads such as polystyrene, polyvinyl alcohol, and polypropylene, finely cut pieces of cellulose, animal and vegetable fibers, etc. can be used. Furthermore, the firing conditions are not particularly limited, but for example, from room temperature to about 600°C for 2 to 50°C.
By increasing the temperature at a rate of ℃/hour to burn out the pyrolyzable substances, then further increasing the temperature to 900 to 1400℃ at a rate of 100 to 200℃/hour, and then holding the temperature at that temperature for about 3 to 8 hours. , the desired porous calcium phosphate bone grafting material can be obtained. When using the bone substitute material according to the present invention,
For example, after sterilization by autoclaving,
Process it with a sterilized diamond bur or the like while pouring pure water or physiological saline into the desired shape.
All you have to do is fill the bone defect. "Embodiments of the Invention" Example 1 100 g of hydroxyapatite particles with a particle size of 1 to 20 μm, wet-synthesized by a known method, and an average pore size of 6 μm.
5 g of polystyrene beads (manufactured by Sumitomo Chemical Co., Ltd., Fine Pearl), hydrogen peroxide solution (manufactured by Wako Pure Chemical Industries, Ltd.,
(30% concentration) and 160 g of pure water were placed in a polyethylene bag and mixed well by hand. The obtained slurry was transferred to a 200c.c. glass beaker, then placed in a circulating constant temperature dryer and left at 110℃ for 24 hours to foam and
Dry. After this, the dried body was taken out from the beaker and transferred to an electric furnace, and heated at 50°C/100°C from room temperature to 600°C.
Temperature rises in 100 ℃, followed by 100 ℃ from 600℃ to 1200℃
The temperature was raised at a rate of 1,200°C/hour, and then held at 1200°C for 3 hours, and then cooled down to room temperature by furnace cooling. The obtained porous sintered body of hydroxyapatite was cut into a rectangular parallelepiped to obtain a bone grafting material. Table 1 shows the properties of the obtained bone grafting material.

[Table] "Effects of the Invention" As explained above, according to the present invention, a calcium phosphate-based porous bone substitute having continuous pores with an average pore diameter of 0.01 to 2000 μm and independent pores with an average pore diameter of 0.01 to 30 μm Because it is made of a material that has the necessary mechanical strength, it can be easily trimmed before and during implant surgery, and even if it is inserted into a living body after filling in a bone defect, it will not cause macrophages, etc. Because body fluids circulate at the site where the oligophages have attached, the capsule reaction can be effectively prevented without causing the oligophages to judge the foreign body. It is possible to proceed with compounding, and it is possible to provide a bone substitute material that has both excellent processability and biocompatibility.

[Claims]

1 Carbon 0.08% or less, silicon 1.00% or less, manganese 2.00% or less, phosphorus 0.04% or less, sulfur 0.03% or less,
A non-magnetic metal cap made of special steel containing 13% to 15% nickel and 15% to 17% chromium.